The membrane pacemaker hypothesis suggests that composition of cell membranes, especially those of mitochondria, is an important determinant of longevity differences between species - and possibly between individuals within a species as well. One specific proposed mechanism is the degree to which membranes contain unsaturated fatty acids, as these are more vulnerable to oxidative damage. Oxidative damage is connected to aging, but its role is subtle and complex: look back in the archives for an outline of the mitochondrial free radical theory of aging, for example, in which oxidative damage inside cells is only the initiator for a long chain of consequences.
Here researchers make an attempt to demonstrate the relevance of the membrane pacemaker hypothesis by running a life span study in mice wherein membrane unsaturated fatty acid levels are lowered. They achieve the expected results in mouse biochemistry, changes that look a lot like slowing of aging, but without any resulting extension of life - an outcome that they blame on side-effects of the method used:
The membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the β1-blocker atenolol increased the amount of the extracellular-signal-regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer-lived mammals.
The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging-related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity.
Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. We conclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug. The lack of modification of total body and organ weights (except for a decrease in kidney weight) and the absence of detection of variations in food intake indicate that the many observed beneficial effects of atenolol are not due to caloric restriction.